Malignant tumors are the leading cause of Japanese deaths, accounting for about 310,000 deaths a year. In the world, cancer causes death of about six million people a year. Cancer treatments employ surgical resection, anti-cancer agents, radiotherapy, and others. However, these treatment regimens involve problems, such as recurrence, problems in QOL, and in addition, the lack of treatment options in cases of advanced cancer to which these treatments are not administered. As a fourth treatment regimen, immunotherapy for cancer (vaccine therapy) has been eagerly expected for a long time. Clinical studies of peptide vaccines were begun in the world in 1990, when human cancer antigen peptides became identifiable. According to the summarized results of clinical studies by administrating peptides alone or in combined therapies, however, the rate of effectiveness was 2.7% in more than 1,000 cases (Nature Immunology, 2004), and it is turning out that it is difficult to formulate them into pharmaceutical preparations.
The present inventors, on the other hand, have conducted tailor-made peptide vaccine therapy, in which the HLA type and specific immune responses of patients were examined in advance to select a peptide vaccine to be administered, and ascertained that the peptide vaccines are safe and effective. Specifically, clinical effects were observed against brain tumors and cervical cancer by administration of tailor-made peptide vaccines alone (Non-Patent Documents 1 to 3). Moreover, their use in combination with anti-cancer agents resulted in excellent clinical effects and safety being achieved in prostate and pancreas cancers, at levels allowing for formulating them into pharmaceutical preparations (Non-Patent Documents 4 and 5).
The cellular immunity by specific T-cells which are thought to be the principal effector in cancer peptide vaccine therapy is human leukocyte antigen (HLA)-restricted, and based on this, researchers in the world, including the present inventors, have carried out the development of vaccines to be given only to patients having specific HLA types (HLA-A2 and HLA-A24). However, the percentage of patients having these two HLA types is on the order of 40 to 75%, and thus the remaining, 25 to 60% patients having less frequent HLA types cannot be benefit from the effects of peptide vaccines. Therefore, there is a need for research on the development of peptide vaccines which can be applied to cancer patients in the world.
There have already been identified peptides which bind to any of HLA-A24, -A2, -A26, and HLA-A3 supertypes (HLA-A3, -A11, -A31, -A33, and -A68.1) and are capable of inducing HLA-restricted CTLs for the respective HLAs. These peptides have been reported to be useful as peptide vaccines against cancer (Patent Documents 1 to 13 and Non-Patent Documents 1 to 17).
In clinical tests, which are being conducted by the present inventor, of cancer vaccines using tailor-made peptides, based on these findings, the HLA type of a patient is examined beforehand, and according to the HLA type of the patient, a maximum four peptides are selected from candidate peptides and administered. Thus, when the HLA type of a patient is HLA-A2-A24, peptides are selected from sets of 8 peptides for HLA-A2 and HLA-A24, respectively, that is 16 peptides. In the case where a patient is homozygous for HLA-A24, however, peptides should be selected among 8 peptides for A24. It is very difficult to introduce additional types of peptides which can be cancer vaccines. Therefore, by determining whether peptides can induce HLA-restricted CTLs across different groups, the choice of peptides can be expanded for patients having specific HLA types.
Meanwhile, pathological mechanism of hepatocellular disorders after hepatitis C virus (HCV) infection is not yet understood well, but many lines of evidence show that virus-specific cytotoxic T lymphocytes (CTLs) may play a key role on disorders of the liver after HCV infection (Non-Patent Document 6). It is also suggested that CTLs are effective for limiting spreading of the virus and eliminating the virus during viral infection (Non-Patent Document 7). Therefore, the induction of CTLs with vaccines would be a promising strategy for controlling diseases associated with HCV infection. Thus, there is a need for developing peptide vaccines which are intended to induce CTLs, because of their reduced cost and storage with ease.
The present inventors previously observed that the C35-44 peptide, a peptide derived from the sequence of the HCV core protein, of which the sequence is YLLPRRGPRL (SEQ ID NO: 25), can induce CTLs in patients positive for HLA-A24 or -A3 supertype (Patent Document 14). Prior to this observation, this C35-44 peptide had also been reported to be capable of strong induction of CTLs useful for eliminating the virus from the peripheral blood of HLA-A2 positive individuals (Non-Patent Document 8 and Patent Document 15).
The documents cited in the present invention are as listed below. The documents described below are incorporated in this patent application by reference.    Patent Document 1: International Publication No. WO 2005/071075    Patent Document 2: International Publication No. WO 01/011044    Patent Document 3: Japanese Unexamined Patent Publication (Kokai) No. 2003-270    Patent Document 4: International Publication No. WO 2003/050140    Patent Document 5: Japanese Unexamined Patent Publication (Kokai) No. Hei 11-318455 (1999)    Patent Document 6: International Publication No. WO 00/12701    Patent Document 7: International Publication No. WO 02/010369    Patent Document 8: International Publication No. WO 99/67288    Patent Document 9: Japanese Patent Application No. 2007-2127179    Patent Document 10: Japanese Unexamined Patent Publication (Kokai) No. 2004-216    Patent Document 11: International Publication No. WO 2007/000935    Patent Document 12: International Publication No. WO 2005/075646    Patent Document 13: International Publication No. WO 2008/007711    Patent Document 14: International Publication No. WO 2007/083807    Patent Document 15: International Publication No. WO 2007/049394    Non-Patent Document 1: Yajima N et al., Clin Cancer Res. 2005 Aug. 15; 11(16):5900-11    Non-Patent Document 2: Mochizuki K et al., Int J Oncol. 2004 July; 25(1):121-31    Non-Patent Document 3: Tsuda N et al., J Immunother. 2004 January-February; 27(1):60-72    Non-Patent Document 4: Inoue Y et al., J Urol. 2001 October; 166(4):1508-13. Erratum in: J Urol. 2002 May; 167(5):2146    Non-Patent Document 5: Yanagimoto H et al., Cancer Sci. 2007 April; 98(4): 605-11. Epub 2007 Feb. 19    Non-Patent Document 6: Chang K M et al, Springer Semin Immunopathol. 1997; 19:57-68    Non-Patent Document 7: Kurokohchi K et al., J. Virol. 1996; 70:232-240    Non-Patent Document 8: Takao Y. et al., Microbiol. Immunol., 48(7), 507-517, 2004    Non-Patent Document 9: Yamada A et al., Cancer Res. 2001 Sep. 1; 61(17):6459-66    Non-Patent Document 10: Kobayashi K et al., Cancer Sci. 2003 July; 94 (7):622-7    Non-Patent Document 11: Nakao M et al., J Immunol. 2000 Mar. 1; 164 (5):2565-74    Non-Patent Document 12: Harashima N et al., Eur J Immunol. 2001 February; 31(2):323-32    Non-Patent Document 13: Minami T et al., Cancer Immunol. Immunother. 2007, May 56(5) 689-98    Non-Patent Document 14: Matsueda S et al., Clin Cancer Res. 2005 Oct. 1; 11(19 Pt 1):6933-43    Non-Patent Document 15: Takedatsu H et al., Clin Cancer Res. 2004 Feb. 1; 10(3):1112-20    Non-Patent Document 16: Naito M et al., Br J Cancer. 2007 Dec. 17; 97(12):1648-54. Epub 2007 Nov. 27